The overall goal of this project is to study the metabolism of endothelial cells (EC) in homeostasis and to document any role EC play in the pathophysiologic sequence of acute respiratory failure. An intrinsic part of this project is to demonstrate that EC cells in culture respond metabolically to substances in a manner that parallels EC response in situ. Specifically, we wish to document that: 1) EC are actively involved in maintaining normal circulating levels of vasoactive substances, 2) that a primary event in respiratory failure is a change in the pulmonary endothelium resulting in abnormal titers of substances which affect the blood vessels and heart, 3) platelets or platelet secretions interact with endothelial cells apart from thrombosis and hemostasis, and stimulate second messengers to initiate mitosis following endothelial damage or in EC growing in culture, and to regulate normal homeostatic EC function, such as enzyme (cyclase) activity by stimulus-secretion coupling.